During the past decade, genetically modified mice have increasingly been a source of many new cancer models that have helped elucidate pathways contributing to tumor development and progression. With the completion of the human and mouse genome sequences and the initiation of large-scale efforts to functionally annotate these genomes, this trend continues to accelerate. Production of genetically modified mice requires highly specialized instrumentation and expertise not available in most labs. The mission of the Gene Targeting and Transgenic Shared Resource (GTTR) is to ensure that investigators have access to state-of-the-art transgenic mouse technologies, methods and animal models. The Resource Director and Assistant Director provide guidance to investigators from the earliest planning stages of the project when constructs are designed to advanced stages of the project during phenotype analysis. Resource technicians perform the specialized ES cell and embryo manipulation methods to generate the genetically modified mice. During the past fourteen years, the Facility has provided over 700 new genetically modified lines. Shared Resource staff have generated mutant mice on multiple strain backgrounds, generated 200 knockouts and 520 transgenics (including BACs) from 165 constructs for the six CCSG Programs. GTTR has also assisted in the development of unique mouse models that contribute to understanding imprinting and its role in cancer, regulation of important genes and two transgenic models that mimic chromosome rearrangements associated with specific human cancers. Use of the Resource has continued to increase with the ongoing recruitment into the Genetics, Cell Stress and Biophysical Therapies, Genitourinary Cancers and Experimental Therapeutics Programs. Projects requiring the development of transgenic mouse models are becoming increasingly relevant to validate in vitro findings, especially in light of high-throughput clinical-based findings. As such, the GTTR has been seeing an increasing trend in the use of the Resource by clinical researchers as well as basic scientists. First priority for use is given to peer-review-funded CCSG members; second to non-peer-review-funded CCSG members; third to non-members and academic collaborators; and last priority to external users. During the reporting period, the Gene Targeting and Transgenic Shared Resource has served 28 members from 5 research programs, with 15% utilization by CCSG members with peer reviewed funding. The CCSG support provides 11% of the overall proposed budget.